TY - JOUR
T1 - Causes of severe pneumonia requiring hospital admission in children without HIV infection from Africa and Asia
T2 - the PERCH multi-country case-control study
AU - O'Brien, Katherine L.
AU - Baggett, Henry C.
AU - Brooks, W. Abdullah
AU - Feikin, Daniel R.
AU - Hammitt, Laura L.
AU - Higdon, Melissa M.
AU - Howie, Stephen R.C.
AU - Deloria Knoll, Maria
AU - Kotloff, Karen L.
AU - Levine, Orin S.
AU - Madhi, Shabir A.
AU - Murdoch, David R.
AU - Prosperi, Christine
AU - Scott, J. Anthony G.
AU - Shi, Qiyuan
AU - Thea, Donald M.
AU - Wu, Zhenke
AU - Zeger, Scott L.
AU - Adrian, Peter V.
AU - Akarasewi, Pasakorn
AU - Anderson, Trevor P.
AU - Antonio, Martin
AU - Awori, Juliet O.
AU - Baillie, Vicky L.
AU - Bunthi, Charatdao
AU - Chipeta, James
AU - Chisti, Mohammod Jobayer
AU - Crawley, Jane
AU - DeLuca, Andrea N.
AU - Driscoll, Amanda J.
AU - Ebruke, Bernard E.
AU - Endtz, Hubert P.
AU - Fancourt, Nicholas
AU - Fu, Wei
AU - Goswami, Doli
AU - Groome, Michelle J.
AU - Haddix, Meredith
AU - Hossain, Lokman
AU - Jahan, Yasmin
AU - Kagucia, E. Wangeci
AU - Kamau, Alice
AU - Karron, Ruth A.
AU - Kazungu, Sidi
AU - Kourouma, Nana
AU - Kuwanda, Locadiah
AU - Kwenda, Geoffrey
AU - Li, Mengying
AU - Machuka, Eunice M.
AU - Mackenzie, Grant
AU - Mahomed, Nasreen
AU - Maloney, Susan A.
AU - McLellan, Jessica L.
AU - Mitchell, Joanne L.
AU - Moore, David P.
AU - Morpeth, Susan C.
AU - Mudau, Azwifarwi
AU - Mwananyanda, Lawrence
AU - Mwansa, James
AU - Silaba Ominde, Micah
AU - Onwuchekwa, Uma
AU - Park, Daniel E.
AU - Rhodes, Julia
AU - Sawatwong, Pongpun
AU - Seidenberg, Phil
AU - Shamsul, Arifin
AU - Simões, Eric A.F.
AU - Sissoko, Seydou
AU - Wa Somwe, Somwe
AU - Sow, Samba O.
AU - Sylla, Mamadou
AU - Tamboura, Boubou
AU - Tapia, Milagritos D.
AU - Thamthitiwat, Somsak
AU - Toure, Aliou
AU - Watson, Nora L.
AU - Zaman, Khalequ
AU - Zaman, Syed M.A.
N1 - Funding Information:
The PERCH study was supported by grant 48968 from the Bill & Melinda Gates Foundation to the International Vaccine Access Center, Department of International Health, Johns Hopkins Bloomberg School of Public Health (Baltimore, MD, USA). JAGS was supported by a clinical fellowship from the Wellcome Trust (UK; 098532). We gratefully acknowledge the substantial contributions to the design of the study by the Pneumonia Methods Working Group (Zulfiqar A Bhutta, Robert E Black, Harry Campbell, Thomas Cherian, Derrick Crook, Menno D de Jong, Scott F Dowell, Stephen M Graham, Keith P Klugman, Claudio F Lanata, Shabir A Madhi, Paul Martin, James Nataro, Franco Piazza, Shamim Ahmed Qazi, Heather Zar) and the PERCH Site Selection Committee (David L Blazes, Robert Bollinger, Claire V Broome, John A Crump, Olivier Fontaine, Robert Gie, David Goldblatt, Patrick W Kelley, Sharon J Peacock, Mark S Riddle, Montse Soriano-Gabarró, Annelies Van Rie, Christopher W Woods). The PERCH Expert Group (William C Blackwelder, Harry Campbell, John A Crump, Menno D de Jong, Adegoke Falade, Claudio F Lanata, Kim Mulholland, Shamim Ahmed Qazi, Cynthia G Whitney) provided valuable advice during the conduct of the study and the analysis of the results for which we are indebted. We also recognise the support provided by the Institutional Review Boards for study oversight. We appreciate the helpful discussions with our many colleagues who were conducting aetiology studies of pneumonia, neonatal sepsis, and diarrhoea during the same period, including the EPIC study, the GABRIEL study, the ANISA study, and the GEMS study. We acknowledge the work of all PERCH contributors who were involved in data collection at the local sites and central laboratories, members of the PERCH Chest Radiograph Reading Panel (see appendix for the list of members in each group), and Shalika Jayawardena and Rose Watt from Canterbury Health Laboratories. Finally, we gratefully recognise the willingness and confidence in the study by the parents of the participating children and express our gratitude for their commitment to the advancement of knowledge toward better health for children of their community and those of other communities. This paper is published with the permission of the Director of the Kenya Medical Research Institute. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the US Centers for Disease Control and Prevention, US Department of Health and Human Services, or the US Government.
Funding Information:
The PERCH study was supported by grant 48968 from the Bill & Melinda Gates Foundation to the International Vaccine Access Center, Department of International Health, Johns Hopkins Bloomberg School of Public Health (Baltimore, MD, USA). JAGS was supported by a clinical fellowship from the Wellcome Trust (UK; 098532). We gratefully acknowledge the substantial contributions to the design of the study by the Pneumonia Methods Working Group (Zulfiqar A Bhutta, Robert E Black, Harry Campbell, Thomas Cherian, Derrick Crook, Menno D de Jong, Scott F Dowell, Stephen M Graham, Keith P Klugman, Claudio F Lanata, Shabir A Madhi, Paul Martin, James Nataro, Franco Piazza, Shamim Ahmed Qazi, Heather Zar) and the PERCH Site Selection Committee (David L Blazes, Robert Bollinger, Claire V Broome, John A Crump, Olivier Fontaine, Robert Gie, David Goldblatt, Patrick W Kelley, Sharon J Peacock, Mark S Riddle, Montse Soriano-Gabarr?, Annelies Van Rie, Christopher W Woods). The PERCH Expert Group (William C Blackwelder, Harry Campbell, John A Crump, Menno D de Jong, Adegoke Falade, Claudio F Lanata, Kim Mulholland, Shamim Ahmed Qazi, Cynthia G Whitney) provided valuable advice during the conduct of the study and the analysis of the results for which we are indebted. We also recognise the support provided by the Institutional Review Boards for study oversight. We appreciate the helpful discussions with our many colleagues who were conducting aetiology studies of pneumonia, neonatal sepsis, and diarrhoea during the same period, including the EPIC study, the GABRIEL study, the ANISA study, and the GEMS study. We acknowledge the work of all PERCH contributors who were involved in data collection at the local sites and central laboratories, members of the PERCH Chest Radiograph Reading Panel (see appendix for the list of members in each group), and Shalika Jayawardena and Rose Watt from Canterbury Health Laboratories. Finally, we gratefully recognise the willingness and confidence in the study by the parents of the participating children and express our gratitude for their commitment to the advancement of knowledge toward better health for children of their community and those of other communities. This paper is published with the permission of the Director of the Kenya Medical Research Institute. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the US Centers for Disease Control and Prevention, US Department of Health and Human Services, or the US Government.
Publisher Copyright:
© 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license
PY - 2019/8/31
Y1 - 2019/8/31
N2 - Background: Pneumonia is the leading cause of death among children younger than 5 years. In this study, we estimated causes of pneumonia in young African and Asian children, using novel analytical methods applied to clinical and microbiological findings. Methods: We did a multi-site, international case-control study in nine study sites in seven countries: Bangladesh, The Gambia, Kenya, Mali, South Africa, Thailand, and Zambia. All sites enrolled in the study for 24 months. Cases were children aged 1–59 months admitted to hospital with severe pneumonia. Controls were age-group-matched children randomly selected from communities surrounding study sites. Nasopharyngeal and oropharyngeal (NP-OP), urine, blood, induced sputum, lung aspirate, pleural fluid, and gastric aspirates were tested with cultures, multiplex PCR, or both. Primary analyses were restricted to cases without HIV infection and with abnormal chest x-rays and to controls without HIV infection. We applied a Bayesian, partial latent class analysis to estimate probabilities of aetiological agents at the individual and population level, incorporating case and control data. Findings: Between Aug 15, 2011, and Jan 30, 2014, we enrolled 4232 cases and 5119 community controls. The primary analysis group was comprised of 1769 (41·8% of 4232) cases without HIV infection and with positive chest x-rays and 5102 (99·7% of 5119) community controls without HIV infection. Wheezing was present in 555 (31·7%) of 1752 cases (range by site 10·6–97·3%). 30-day case-fatality ratio was 6·4% (114 of 1769 cases). Blood cultures were positive in 56 (3·2%) of 1749 cases, and Streptococcus pneumoniae was the most common bacteria isolated (19 [33·9%] of 56). Almost all cases (98·9%) and controls (98·0%) had at least one pathogen detected by PCR in the NP-OP specimen. The detection of respiratory syncytial virus (RSV), parainfluenza virus, human metapneumovirus, influenza virus, S pneumoniae, Haemophilus influenzae type b (Hib), H influenzae non-type b, and Pneumocystis jirovecii in NP-OP specimens was associated with case status. The aetiology analysis estimated that viruses accounted for 61·4% (95% credible interval [CrI] 57·3–65·6) of causes, whereas bacteria accounted for 27·3% (23·3–31·6) and Mycobacterium tuberculosis for 5·9% (3·9–8·3). Viruses were less common (54·5%, 95% CrI 47·4–61·5 vs 68·0%, 62·7–72·7) and bacteria more common (33·7%, 27·2–40·8 vs 22·8%, 18·3–27·6) in very severe pneumonia cases than in severe cases. RSV had the greatest aetiological fraction (31·1%, 95% CrI 28·4–34·2) of all pathogens. Human rhinovirus, human metapneumovirus A or B, human parainfluenza virus, S pneumoniae, M tuberculosis, and H influenzae each accounted for 5% or more of the aetiological distribution. We observed differences in aetiological fraction by age for Bordetella pertussis, parainfluenza types 1 and 3, parechovirus–enterovirus, P jirovecii, RSV, rhinovirus, Staphylococcus aureus, and S pneumoniae, and differences by severity for RSV, S aureus, S pneumoniae, and parainfluenza type 3. The leading ten pathogens of each site accounted for 79% or more of the site's aetiological fraction. Interpretation: In our study, a small set of pathogens accounted for most cases of pneumonia requiring hospital admission. Preventing and treating a subset of pathogens could substantially affect childhood pneumonia outcomes. Funding: Bill & Melinda Gates Foundation.
AB - Background: Pneumonia is the leading cause of death among children younger than 5 years. In this study, we estimated causes of pneumonia in young African and Asian children, using novel analytical methods applied to clinical and microbiological findings. Methods: We did a multi-site, international case-control study in nine study sites in seven countries: Bangladesh, The Gambia, Kenya, Mali, South Africa, Thailand, and Zambia. All sites enrolled in the study for 24 months. Cases were children aged 1–59 months admitted to hospital with severe pneumonia. Controls were age-group-matched children randomly selected from communities surrounding study sites. Nasopharyngeal and oropharyngeal (NP-OP), urine, blood, induced sputum, lung aspirate, pleural fluid, and gastric aspirates were tested with cultures, multiplex PCR, or both. Primary analyses were restricted to cases without HIV infection and with abnormal chest x-rays and to controls without HIV infection. We applied a Bayesian, partial latent class analysis to estimate probabilities of aetiological agents at the individual and population level, incorporating case and control data. Findings: Between Aug 15, 2011, and Jan 30, 2014, we enrolled 4232 cases and 5119 community controls. The primary analysis group was comprised of 1769 (41·8% of 4232) cases without HIV infection and with positive chest x-rays and 5102 (99·7% of 5119) community controls without HIV infection. Wheezing was present in 555 (31·7%) of 1752 cases (range by site 10·6–97·3%). 30-day case-fatality ratio was 6·4% (114 of 1769 cases). Blood cultures were positive in 56 (3·2%) of 1749 cases, and Streptococcus pneumoniae was the most common bacteria isolated (19 [33·9%] of 56). Almost all cases (98·9%) and controls (98·0%) had at least one pathogen detected by PCR in the NP-OP specimen. The detection of respiratory syncytial virus (RSV), parainfluenza virus, human metapneumovirus, influenza virus, S pneumoniae, Haemophilus influenzae type b (Hib), H influenzae non-type b, and Pneumocystis jirovecii in NP-OP specimens was associated with case status. The aetiology analysis estimated that viruses accounted for 61·4% (95% credible interval [CrI] 57·3–65·6) of causes, whereas bacteria accounted for 27·3% (23·3–31·6) and Mycobacterium tuberculosis for 5·9% (3·9–8·3). Viruses were less common (54·5%, 95% CrI 47·4–61·5 vs 68·0%, 62·7–72·7) and bacteria more common (33·7%, 27·2–40·8 vs 22·8%, 18·3–27·6) in very severe pneumonia cases than in severe cases. RSV had the greatest aetiological fraction (31·1%, 95% CrI 28·4–34·2) of all pathogens. Human rhinovirus, human metapneumovirus A or B, human parainfluenza virus, S pneumoniae, M tuberculosis, and H influenzae each accounted for 5% or more of the aetiological distribution. We observed differences in aetiological fraction by age for Bordetella pertussis, parainfluenza types 1 and 3, parechovirus–enterovirus, P jirovecii, RSV, rhinovirus, Staphylococcus aureus, and S pneumoniae, and differences by severity for RSV, S aureus, S pneumoniae, and parainfluenza type 3. The leading ten pathogens of each site accounted for 79% or more of the site's aetiological fraction. Interpretation: In our study, a small set of pathogens accounted for most cases of pneumonia requiring hospital admission. Preventing and treating a subset of pathogens could substantially affect childhood pneumonia outcomes. Funding: Bill & Melinda Gates Foundation.
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U2 - 10.1016/S0140-6736(19)30721-4
DO - 10.1016/S0140-6736(19)30721-4
M3 - Article
C2 - 31257127
AN - SCOPUS:85069522084
SN - 0140-6736
VL - 394
SP - 757
EP - 779
JO - The Lancet
JF - The Lancet
IS - 10200
ER -